Abstract
The development of an effective vaccine against Mycobacterium tuberculosis is a research area of intense interest. Mounting evidence suggests that protective immunity to M. tuberculosis relies on both MHC class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells. By purifying polypeptides present in the culture filtrate of M. tuberculosis and evaluating these molecules for their ability to stimulate PBMC from purified protein derivative-positive healthy individuals, we previously identified a low-m.w. immunoreactive T cell Ag, Mtb 8.4, which elicited strong Th1 T cell responses in healthy purified protein derivative-positive human PBMC and in mice immunized with recombinant Mtb 8.4. Herein we report that Mtb 8.4-specific T cells can be detected in mice immunized with the current live attenuated vaccine, Mycobacterium bovis-bacillus Calmette-Guérin as well as in mice infected i.v. with M. tuberculosis. More importantly, immunization of mice with either plasmid DNA encoding Mtb 8.4 or Mtb 8.4 recombinant protein formulated with IFA elicited strong CD4(+) T cell and CD8(+) CTL responses and induced protection on challenge with virulent M. tuberculosis. Thus, these results suggest that Mtb 8.4 is a potential candidate for inclusion in a subunit vaccine against TB.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies, Bacterial / biosynthesis
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Antigens, Bacterial / administration & dosage*
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Antigens, Bacterial / immunology
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BCG Vaccine / administration & dosage*
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BCG Vaccine / immunology
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Bacterial Proteins*
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Cells, Cultured
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Cytotoxicity Tests, Immunologic
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DNA, Bacterial / administration & dosage
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DNA, Bacterial / immunology
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Epitopes, T-Lymphocyte / immunology
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Immunoglobulin G / biosynthesis
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Injections, Subcutaneous
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Interferon-gamma / biosynthesis
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Lymphocyte Activation
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Macrophages / immunology
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Macrophages / microbiology
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Mice
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Mice, Inbred C57BL
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Mycobacterium bovis / immunology
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Mycobacterium tuberculosis / immunology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / microbiology
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T-Lymphocytes, Cytotoxic / immunology
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T-Lymphocytes, Cytotoxic / microbiology
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Th1 Cells / immunology
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Th1 Cells / microbiology
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Tuberculosis / immunology
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Tuberculosis / prevention & control*
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / immunology
Substances
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Antibodies, Bacterial
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Antigens, Bacterial
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BCG Vaccine
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Bacterial Proteins
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DNA, Bacterial
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Epitopes, T-Lymphocyte
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Immunoglobulin G
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Mtb8.4 protein, Mycobacterium tuberculosis
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Vaccines, DNA
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Vaccines, Synthetic
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Interferon-gamma